Society of Environmental Toxicology and Chemistry (SETAC) Pellston Workshop
Advancing the Adverse Outcome Pathway Concept: An International Horizon Scanning Approach

A Pellston Workshop that focused on advancing the adverse outcome pathway framework was held in April 2017 in Cornwall, Ontario, Canada, and co-chaired by Dr. Carlie LaLone, (US Environmental Protection Agency) and Dr. Markus Hecker (University of Saskatchewan). This workshop involved thirty-eight cross-sector participants from North America, Europe, and Asia, including 4 post-doctoral fellows and one graduate student.

Since the original publication on the adverse outcome pathway (AOP) concept (Ankley et al. 2010 Environmental Toxicology and Chemistry, 29(3):730-741), the framework has matured significantly and has increasingly been recognized as a powerful approach for organizing pathway information in a format applicable for regulatory decision-making. With increasing interest in and uptake of the AOP framework, a need was identified to engage the global scientific and regulatory communities in identifying future directions for the framework. Therefore, as a means to reach beyond current stakeholders, the SETAC Pellston Workshop was initiated and developed based on input collected from a global Horizon Scanning exercise, where a survey asked participants to propose questions that identify key outstanding challenges or limitations that must be addressed in order to realize the full potential of the AOP framework in research and regulatory decision-making.

The Horizon Scanning exercise led to the collection of 340 valid questions that were subjected to an expert ranking exercise conducted by the steering committee (13 members) of the Pellston Workshop. A description of the Horizon Scanning approach and expert ranking exercise can be found in a recently published ET&C Focus Topic Article (LaLone et al., 2017 Environmental Toxicology and Chemistry, 36(6):1411-1421). This expert ranking exercise resulted in the identification of four core themes that were addressed during the Pellston Workshop:

1) AOP networks and their applications

2) Quantitative AOPs and their applications

3) Regulatory use of the AOP framework

4) Roadmap to expand awareness of, involvement in, and application of the AOP framework and AOP knowledgebase in the broader scientific and regulatory/environmental policy communities

Manuscripts are being developed from discussions held at the Pellston Workshop that focus on addressing these core themes.

Below are the authors and titles of papers to be submitted as products of the Workshop (Note: three have been accepted for publication or published):

1. Knapen, D., Angrish, M., Fortin, M., Katsiadaki, I., Leonard, M., Margiotta-Casaluci, L., Munn, S., O’Brien, J., Pollesch, N., Smith, C., Zhang, X., and Villeneuve D. L. (2018) Adverse Outcome Pathway Networks I: Development and Applications. Environmental Toxicology and Chemistry. Accepted. DOI: 10.1002/etc.4125

2. Villeneuve D. L., Angrish, M., Fortin, M., Katsiadaki, I., Leonard, M., Margiotta-Casaluci, L., Munn, S., O’Brien, J., Pollesch, N., Smith, C., Zhang, X., and Knapen, D. (2018) Adverse Outcome Pathway Networks II: Network Analytics. Environmental Toxicology and Chemistry. Accepted. DOI: 10.1002/etc.4124

3. Carusi, A., Davies, M.R., De Grandis, G., Escher, B.I., Hodges, G., Leung, K.M.Y., Whelan, M., Willett, C., and Ankley G.T. (2018) Harvesting the promise of AOPs: An assessment and recommendations. Science of the Total Environment 628, 1542-1556. DOI: 10.1016/j.scitotenv.2018.02.015

4. Hecker, M. and LaLone C.A. Adverse Outcome Pathways: Moving from a scientific concept to a globally accepted framework

5. Perkins E.J., Ashauer, R., Conolly, R., Landesmann, B., Mackay, C., Murphy, C., Pollesch, N., Wheeler, J.R., Zupanic, A., Scholz, S. Building and Applying Quantitative Adverse Outcome Pathway Models for Chemical Hazard and Risk Assessment

6. Browne, P., Coady, K., Embry, M., Hill, T., Leinala, E., Steeger, T., Wijkhuizen-Maslankiewicz, L., and Hutchinson, T. Application of Adverse Outcome Pathways in Various Stages of Chemicals Management, including Innovation, Registration, and Stewardship.

In conclusion, the SETAC Pellston Workshop Advancing the Adverse Outcome Pathway Concept: An International Horizon Scanning Approach successfully collected and addressed questions from the global community that were used to establish a road-map to guide future research and regulatory initiatives, identified global issues and key uncertainties regarding the applicability and readiness of the AOP concept to address current regulatory and scientific needs.

Workshop Participants:

Theme (Workgroup) 1: Adverse outcome pathway networks and their applications

Name	Sector	Location
Dries Knapen (leader)	Academia	Belgium
Dan Villeneuve (leader)	Government	US
Sharon Munn	Government	EU
Xiaowei Zhang	Academia	China
Jason O'Brien	Government	Canada
Ioanna Katsiadaki	Government	UK
Luigi Margiotta-Casaluci	Academia	UK
Marc Leonard	Industry	France
Marie Fortin	Industry	US
Michelle Angrish	Postdoc	US
L. Cody Smith	Grad Student	US

Theme (Workgroup) 2: Quantitative adverse outcome pathways and their applications

Name	Sector	Location
Stefan Scholz (leader)	Academia	EU
Ed Perkins (leader)	Government	US
Cameron Mackay	Industry	UK
Cheryl Murphy	Academia	US
Anze Zupanic	Academia	Switzerland
Brigitte Landesmann	Government	EU
Rory Conolly	Government	US
James Wheeler	Industry	UK
Roman Ashauer	Academia	UK
Nathan Pollesch	Postdoc	US

Theme (Workgroup) 3: Regulatory use of the adverse outcome pathway framework

Name	Sector	Location
Katie Coady (leader)	Industry	US
Patience Browne (leader)	OECD	EU
Michelle Embry	Industry	US
Tom Steeger	Government	US
Lidka Wijkhuizen-Maslankiewicz	Government	EU
Eeva Leinala	OECD	EU
Tom Hutchinson	Academia	UK
Thomas Hill	Postdoc	US

Theme (Workgroup) 4: Roadmap to expand awareness of, involvement in, and application of the AOP framework and AOP knowledgebase in the broader scientific and regulatory/environmental policy communities

Name	Sector	Location
Annamaria Carusi (leader)	Academia	UK
Gary Ankley (leader)	Government	US
Maurice Whelan	Government	EU
Kate Willett	NGO	US
Geoff Hodges	Industry	UK
Kenny Leung	Academia	Hong Kong
Beate Escher	Academia	EU
Mark Davies	Industry	UK
Giovanni De Grandis	Postdoc	EU

For more information, contact Pellston workshop co-chairs Dr. Markus Hecker, markus.hecker@usask.ca, or Dr. Carlie LaLone, lalone.carlie@epa.gov